Mailplane: If you like Gmail but don’t want to lose OS X features, Mailplane is a very decent alternative combining the best of gmail with a respectable OS X integration.

Sparrow: A new alternative (only for gmail) that is growing in popularity for its ease of use and iPad-like interface. Although it only works for gmail, the plan is to expand it. Still very beta. Still free. Worth to follow around and check every now and then.

There may be others but these are the most known/used (excluding Mail.app of course). Eudora is also popular, but I believe it’s a little bit outdated.